Chapter 7: Autonomic Nervous System

SNS: Divergence and convergence can be viewed as a way of getting groups of neurons to do the same thing. Give examples of both divergence and convergence in the SNS. What significance might that have regarding the control of postganglionic neurons?

Preganglionic axons typically bifurcate, and may innervate several paravertebral ganglia (divergence). Individual postganglionic neurons are innervated by multiple preganglionics (10 or so; convergence).

The receptors for norepinephrine (or epinephrine, which is also called adrenaline), called adrenergic receptors, are also distinguished based on pharmacological profiles into what two main classes?

alpha-adrenergic receptors and beta-adrenergic receptors, also with multiple subtypes in each class.

eceptors for acetylcholine (ACh), called cholinergic receptors, are not all the same and can be divided into what two general classes? What are the classifications based on?

nicotinic cholinergic receptors and muscarinic cholinergic receptors. This classification was initially based on responses to different pharmacological agonists, nicotine and muscarine.

What are the two divisions of the ANS?

the sympathetic nervous system and the parasympathetic nervous system.

The parasympathetic branch of the ANS:

- Innervates organs and tissues in the thoracic cavity. - Arises from the brainstem and sacral segments of the spinal cord. - Has long pre-ganglionic fibers.

Electrical stimulation of the thoracic spinal cord increases heart rate. Which drug below would antagonize that response?

- propranolol (a beta adrenergic receptor antagonist) - hexamethonium (a ganglionic-type nicotinic cholinergic receptor antagonist)

SNS: Axons of preganglionic neurons leave the cord as part of the ventral roots and do one of three things. What are they?

1] leave the ventral root to synapse in a ganglion adjacent to the spinal column (a paravertebral ganglion) at the level at which the axon exited the cord, [2] pass through the ganglion to ascend or descend to a more distant paravertebral ganglion a segment or a few segments away, or [3] pass through a paravertebral ganglion to synapse more distally within the gut in a prevertebral ganglion (also called collateral ganglia) (e.g., celiac ganglion).

What is the primary neurotransmitter used at each of these peripheral synapses of the somatic motor neurons, preganglionic neurons (SNS and PNS), and parasympathetic post-ganglionic neurons.

Acetylcholine (ACh)

All of the different classes and subtypes of adrenergic receptors are what type of receptor class?

All of the different classes and subtypes of adrenergic receptors are G-protein coupled receptors. The receptors at the sympathetic neuro-effector junction are adrenergic receptors, of the alpha and/or beta variety.

How do the SNS and PNS differ anatomically?

As illustrated in the figure below, the SNS arises from the thoracic and upper lumbar levels of the spinal cord whereas the PNS arises from the brain and the sacral spinal cord. Thus, the SNS is sometimes referred to as the thoraco-lumbar division of the ANS while the PNS is referred to as the cranio-sacral division. The parasympathetic nervous system, or cranio-sacral division, is illustrated in blue. The sympathetic nervous system, or thoraco-lumbar division, is illustrated in red. Note that most tissues receive inputs from both divisions of the autonomic nervous system. (For this class you do not need to learn the names of the specific nerves or ganglia, except for the vagus nerve (Xth cranial nerve), which is the major nerve of the parasympathetic nervous system.)

Although both norepinephrine (NE) and epinephrine (E) are agonists at all of the subtypes of adrenergic receptors, they do not have equal effects on them. What determines the effects that the NT has?

As shown in the table below, at some receptors NE is a more potent agonist than E (e.g., alpha1), whereas at others E is much more potent than NE (e.g., beta2), and others, like the beta1, does not distinguish between E and NE. So, determining what the relative importance of neurally released NE versus hormonally-related E is on different tissues, depends on the particular receptors present. Also, it is clear that the different receptor subtypes are coupled to different G proteins and have different effects on the cell signaling cascades. However, even knowing, for example, whether it causes an increase or decrease in cyclic AMP does little in saying what the physiological effect will be. The table above includes the location of the different types of adrenergic receptors in different visceral tissues, and the effects of stimulating that receptors. In each case these have implications for actions of norepinphrine and epinephrine. For example, the beta2 adrenergic receptors in the airways (bronchi, in the table below), which cause dilation of the airways, would be particularly responsive to epinephrine released from the adrenal medulla. The beta1 adrenergic receptors in the heart respond equally well epinephrine and norepinephrine from either neural or hormonal sources. In contrast, the alpha1 adrenergic receptors in blood vessels, which cause blood vessels to constrict, would be more responsive to norepinephrine release locally from sympathetic nerves. Interestingly, some blood vessels (primarily in some muscles) also have beta2 adrenergic receptors that cause dilation, and so epinephrine released from the adrenal medulla would tend to counteract the constrictor effect of the alpha1 receptors.

Should the definition include visceral afferent nerves or should it be limited to an efferent system?

Classically the ANS is an output system (and we will use the term that way), though some authors now use it more similarly to the terminology of somatic nervous system to include both efferent (output) and afferent (sensory) components arising from visceral tissues

How do the SNS and PNS differ energetically/functionally? How do they work together?

Functionally, we can think about the sympathetic nervous system (SNS) as "ergotropic" or "toward energy use", where as the parasympathetic nervous system (PNS) as "tropotrophic" or "toward growth and energy storage". More typically, this is stated as the SNS is the divsion of the ANS mediating "fight and flight" whereas the PNS is the division mediating "rest and digest". While it should be clear from this description that the SNS and PNS have opposing actions, it is important to think about them as acting in an cooperative fashion; as the activity of one division increases, the other decreases. Thus, during a fight or flight response, SNS activity increases while PNS activity decreases.

In response to increased sympathetic nervous system activity heart: blood vessels: eyes: respiratory tree: digestive tract: adipose tissue: liver: sweat glands: kidney: urinary bladder:

Heart: beats faster and stronger Blood vessels: constrict, and therefore blood pressure goes up (no parasymp) Eyes: pupil widens and eyes "pop out" Respiratory tree: airways dilate Digestive tract: decreased motility and secretion (decreased digestion) Adipose tissue: increased fat breakdown (no parasymp) Liver: make more glucose available (glycogenolysis, gluconeogensis) (no para) Sweat glands: increased sweating (no parasymp) Kidney: increase renin secretion (and increase sodium retention) (no parasymp) Urinary bladder: prevent voiding

Nicotinic and muscarinic receptors are quite different in their structure and how they function. Briefly describe their structure and how they function.

Nicotinic cholinergic receptors are ligand-gated ion channels that are somewhat selective for Na+ ; they are made up of 5 protein subunits though there are different subunits and the receptor properties are somewhat different depending on the nature of the 5 subunits. In contrast, muscarinic cholinergic receptors are G-protein coupled receptors. As shown in the figure above, the ACh receptors present in the autonomic ganglia are of the nicotinic type. The ACh receptors at the somatic neuromuscular junction are also of the nicotinic type, but with a different subunit composition compared to the ones in the autonomic ganglia and therefore with a different pharmacological profile (i.e., some drugs might act at one site but not the other.) The acetylcholine released by the parasympathetic post-ganglionic neurons acts on muscarinic cholinergic receptors. Depending on the nature of the G-protein coupling, acetylcholine acting at the parasympathetic neuroeffector junction could have very different cellular actions. In one type of muscarinic cholinergic receptor we will talk about (i.e., the one in the heart), the G protein is coupled to opening a K+ channel.

What is the primary neurotransmitter of most sympathetic postganglionic neurons?

Norepinephrine (NE) (Note that the cells of the adrenal medulla, which in many ways are like sympathetic postganglionic neurons, release epinephrine and norepinephrine; approximately 80% of the adrenal medullary cells release epinephrine.)

Describe the organization of the PNS

Parasympathetic preganglionic neurons are present in sacral cord (S2-S4), and in discrete regions of the brain associated with 4 of the cranial nerves (III, VII, IX, X). By far, most preganglionic parasympathetic neurons (maybe as much as 95%) are associated with the vagus nerve (cranial nerve X), and have their cell bodies in the medulla oblongata.

Describe the organization of the SNS

SNS preganglionic neurons are located in thoracic and upper lumbar spinal segments (through L2 or L3), primarily in the intermediolateral cell column. Within the thoraco-lumbar cord sympathetic pregangionic neuron column, the entire body is represented in a rostral-caudal manner. (For example, the preganglionic neurons innervating structures in the head are located in the upper thoracic spinal cord.)

T/F: in some cases (none of which we will talk about in this course) it appears that that neither norepinephrine or acetylcholine are involved; this non-adrenergic, non-cholinergic (NANC) transmission appears to occur in some sites in the body.

T

T/F: many of the postganglionic neurons, in addition to using either norepinephrine or acetylcholine as their neurotransmitter also release various other signaling molecules (often peptides) as co-transmitters. While norepinephrine or acetylcholine explain much of the action, these other signaling molecules also play a role.

T

Should the enteric nervous system be included as part of the ANS?

The enteric nervous system is a plexus of nerves associated with the gastrointestinal tract. In one sense it should be considered part of the ANS because it does control smooth muscle and is certainly involuntary. On the other hand, it is not an output system of the CNS, but rather can function independently (though it is under partial regulation by the ANS). Classically, it is not considered part of the ANS.

Describe the two neuron chain of the ANS

The first neuron in this chain, the preganglionic neuron, is located in the CNS and its axon projects out of the CNS to innervate the second neuron in the chain, the postganglionic neuron. These postganglionic neurons are located in clusters, autonomic ganglia, and are part of the peripheral nervous system.

SNS: there are paravertebral ganglia associated with each spinal segment. Collectively, what are they referred to as? How are they connected?

There are paravertebral ganglia associated with each spinal segment, and collectively these are referred to as the sympathetic chain ganglia. As shown in the figure below, these chain ganglia are connected by axons of preganglionic neurons that ascend or descend in the chain to innervate ganglia further rostral or caudal in the chain.

Consider the baroreceptor reflex involved in the control of blood pressure that we mentioned in a previous class, as illustrated in the figure below. Describe how this reflex works and how it shows coordinated of the SNS and PNS

There is sensory input arising from stretch on certain blood vessels and conveyed to the brain via the IXth and Xth cranial nerves (green lines in the figure). And increase in blood pressure is thus signaled to the brain, and through interneurons this is conveyed to parasympathetic preganglionic neurons in the brainstem (red line in the figure), which become more active to slow the heart in response to this increase in blood pressure. The sensory information is also conveyed through interneurons to sympathetic preganglionic neurons (blue lines) that then become less active, thereby slowing the heart and reducing constriction of blood vessels. Thus, sensory input influencing sympathetic and parasympathetic activity in a coordinated manner.

The hypothalamus plays a crucial role in the central neural control of the autonomic nervous system. when we think about the brain systems involved in this, the hypothalamus clearly plays role (see figure below), but what are the inputs to the hypothalamus?

Think limbic system (amygdala, cortical limbic areas).

many autonomic nerves are active under baseline resting conditions. How is this beneficial? How does this differ from somatic motor neurons?

This "tonic activity" (i.e., normal basal tone), allows the activity of these nerves to be modulated either up or down. While is is critically important for the functioning of the autonomic nervous system, the origin of this basal tone is not well understood. [This is in distinct contrast to the somatic motor system; somatic motor neurons are inactive at rest.]

Most tissues innervated by the ANS are innervated by both divisions. Why would having such dual innervation be useful useful? What does having dual controllers suggest about integration? However, some tissues are innervated by only the sympathetic division of the ANS; e.g., kidneys, spleen, blood vessels are innervated by only the SNS. (What might the single innervation here say about the regulation of these tissues?)

[Think about the greater degree of control by dual controls systems; consider a car that has both a gas pedal and a brake pedal.) [Think about integration; consider the car example again, and the coordination required for the gas pedal and brake pedal.)

Norepinephrine is an agonist at which of the following receptors

alpha1 adrenergic receptors, beta2 adrenergic receptors

All of the neurons that project out of the CNC are cholinergic/adrenergic

cholinergic

What are neurons that use acetylcholine often referred to as? Neurons that use norepinephrine?

cholinergic neurons; noradrenergic (or adrenergic)

Which of the following tissues is only innervated by the sympathetic NS?

kidney and liver

What is one notable exception to sympathetic postganglionic neurons releasing norepinephrine

the sympathetic neurons innervating sweat glands, which release acetylcholine instead.

Which nerve provides parasympathetic control of the heart?

the vagus nerve (cranial nerve X)

The autonomic nervous system is the portion of the nervous system that innverates

visceral tissues and organs. The ANS innervates smooth muscle, cardiac muscle, and glands (both exocrine and endocrine); it innervates all effector tissues except skeletal muscle cells